Project Summary This project will create and assess new optical imaging and computational technologies with the goal of improving the detection rates of precancerous, non-polypoid lesions during colonoscopy screening. Identifying and removing these subtle lesions is critical to improving the protective value of colonoscopy in reducing mortality from colorectal cancer. However, current approaches to non-polypoid lesion detection are largely unsuccessful because they are time-consuming and require specialized training (chromoendoscopy), or they start with poor image contrast (software analysis of conventional video). This project focuses on developing a novel technique, called quantitative topographic endoscopy (QTE), that optically measures colon surface properties via a modified commercial colonoscope. The key innovation in this proposal is to utilize structured illumination and build on concepts from computer vision and optical engineering to acquire high-resolution 3D images of the colon surface through a custom endoscope. The project will be implemented through three specific aims: (1) develop a miniaturized, quantitative, high-resolution topography system, (2) implement QTE in a modified commercial colonoscope ready for clinical testing, and (3) determine the validity of QTE in a phantom model and its clinical feasibility in a pilot human study. QTE systems developed in this project will be tested in tissue-mimicking phantoms with a goal of achieving better than 1-mm height sensitivity, in ex-vivo resected colon samples with a goal of accurately reconstructing surface shapes from a complex tissue, and in a pilot human study with the goal of obtaining surface topography non-polypoid lesions. Beyond increasing non-polypoid lesion detection rates, QTE has the potential to address other limitations of colonoscopy, including preventing missed polypoid lesions, classifying lesions for resect-and-discard strategies, and improving colonoscopy quality metrics. Additionally, the development of a QTE system that is approved for human studies will serve as a platform for future clinical assessment of other optical techniques such as spatial frequency domain imaging and speckle imaging in a variety of gastroenterology applications.